Kidney Week

Abstract: FR-PO059

Neonatal AKI in a Juvenile Rabbit Model Results in Reduced Nephron Number Assessed by MRI

Session Information

• AKI: Tubules, Metabolism, New Models
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Charlton, Jennifer R., University of Virginia, Charlottesville, Virginia, United States

Jennifer R. Charlton,

• Baldelomar, Edwin, University of Hawaii at Manoa, Honolulu, Hawaii, United States

Edwin Baldelomar,

• Nam, Sejin, University of Hawaii at Manoa, Honolulu, Hawaii, United States

Sejin Nam,

• Bennett, Kevin M., University of Hawai'i, Honolulu, Hawaii, United States

Kevin M. Bennett,

Background

Acute kidney injury (AKI) affects 30% of preterm neonates. Preterm neonates develop AKI during nephrogenesis conferring a risk for chronic kidney disease. Current monitoring practices cannot detect microstructural changes in the kidney. Our objective was to assess if the renal microstructure, number (N_glom) and volume (V_glom) of the glomeruli, is affected by AKI during nephrogenesis using cationic ferritin enhanced MRI (CFE-MRI).

Methods

New Zealand rabbits were used as nephrogenesis occurs for 3 postnatal weeks. The AKI group received indomethacin and gentamicin at week #1 for four days. At six weeks, the AKI and control groups (5/grp) were injected with cationic ferritin, euthanized and kidneys were imaged (7T ClinScan GRE pulse sequence:TR:80/TE:20, thickness 0.17, FOV 29, 448*448 matrix, FA 25^o). N_glom and V_glom were determined by threshold guiding with a watershed transformation.

Results

Body and kidney weights were significantly lower in the AKI group. The kidney/body weight and renal function measured by serum creatinine was not different between the groups. N_glom and V_glom were lower in the AKI group (N_glom: 86387 vs 178093, p=0.01; V_glom: 319044 vs. 425029 μm³, p=0.01), Fig 1. AKI kidneys had a layer of glomeruli which were not labeled and undetectable by MRI. On histological assessment, the glomeruli in the undetectable region were shrunken, immature and lacked tubules (Fig 2).

Conclusion

Neonatal AKI from gentamicin and indomethacin causes permanent glomerular reduction without glomerular hypertrophy. Tools such as CFE-MRI that allow us to visualize and quantify renal microstructure to detect early CKD and evaluate the nephrotoxic potential of medications during nephrogenesis.

Funding

• Private Foundation Support